4-88662533-C-T

Variant names:

• chr4-88662533-C-T
• NM_014606.3:c.1249C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014606.3(HERC3):​c.1249C>T​(p.His417Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HERC3 NM_014606.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.77

Genes affected

HERC3 (HGNC:4876): (HECT and RLD domain containing E3 ubiquitin protein ligase 3) This gene encodes a member the HERC ubiquitin ligase family. The encoded protein is located in the cytosol and binds ubiquitin via a HECT domain. Mutations in this gene have been associated with colorectal and gastric carcinomas. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]

HERC3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18309018).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HERC3	NM_014606.3	c.1249C>T	p.His417Tyr	missense_variant	Exon 11 of 26	ENST00000402738.6	NP_055421.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HERC3	ENST00000402738.6	c.1249C>T	p.His417Tyr	missense_variant	Exon 11 of 26	1	NM_014606.3	ENSP00000385684.1
HERC3	ENST00000264345.7	c.1249C>T	p.His417Tyr	missense_variant	Exon 9 of 24	1
HERC3	ENST00000512194.2	c.1249C>T	p.His417Tyr	missense_variant	Exon 12 of 26	5		ENSP00000421021.2
HERC3	ENST00000470815.1	n.224+4042C>T		intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T;T
Eigen	Benign	0.043
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.76	D
LIST_S2	Uncertain	0.90	.;D
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.55	N;N
REVEL	Benign	0.085
Sift	Benign	0.083	T;T
Sift4G	Benign	0.10	T;T
Polyphen		0.59	P;P
Vest4		0.29
MutPred		0.36		Loss of disorder (P = 0.0419);Loss of disorder (P = 0.0419);
MVP		0.14
MPC		0.70
ClinPred		0.71	D
GERP RS		4.6
Varity_R		0.11
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-89583684;